Twenty somethig years of analyzing HLA Class I/II antigens with mass spectrometry and we need to face facts -- mass spectrometry of these things still sucks. Important? Yes. Super incredibly important. But mobile protons are NOT a fun thing for us to work with as our exclusive charge acceptor. Our technologies work best with doubly charged peptides that end in lysines or arginines.
But LCMS is the only thing that has ever worked at all for these molecules, so we're stuck with them. What we need is a set of guidelines to at least reference --- and here is the first one I've seen!
Honestly, I expected this to have maybe 50 different authors on it as some sort of an over arching consensus of a big meeting on the topic to sort it out. And, that might make me a little more comfortable, but I tell you what, this document is not bad at all. You know why?
This group has actually validated some HLA peptides and successfully utilized them! This isn't a big hypothetical piece. This is the next stage beyond where most of us have been going. I came out thinking it was really sobering. On our side we're pressured to find more and more of these peptide identifications and hitting so many hundred or thousand is the only metric we have. We don't need to find 1,500 mediocre peptides. We need to find the one really good one that differs in the cell type you want to target. This isn't a long read and if you're doing these kinds of studies, I 100% recommend it.
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